Structural basis for the regulation of inositol trisphosphate receptors by Ca2(+) and IP(3) Journal Article
| Authors: | Paknejad, N.; Hite, R. K. |
| Article Title: | Structural basis for the regulation of inositol trisphosphate receptors by Ca2(+) and IP(3) |
| Abstract: | Inositol trisphosphate receptors (IP3Rs) are ubiquitous Ca2+-permeable channels that mediate release of Ca2+ from the endoplasmic reticulum, thereby regulating numerous processes including cell division, cell death, differentiation and fertilization. IP3Rs are jointly activated by inositol trisphosphate (IP3) and their permeant ion, Ca2+. At high concentrations, however, Ca2+ inhibits activity, ensuring precise spatiotemporal control over intracellular Ca2+. Despite extensive characterization of IP3R, the mechanisms through which these molecules control channel gating have remained elusive. Here, we present structures of full-length human type 3 IP3Rs in ligand-bound and ligand-free states. Multiple IP3-bound structures demonstrate that the large cytoplasmic domain provides a platform for propagation of long-range conformational changes to the ion-conduction gate. Structures in the presence of Ca2+ reveal two Ca2+-binding sites that induce the disruption of numerous interactions between subunits, thereby inhibiting IP3R. These structures thus provide a mechanistic basis for beginning to understand the regulation of IP3R. © 2018, The Author(s). |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 25 |
| Issue: | 8 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-08-01 |
| Start Page: | 660 |
| End Page: | 668 |
| Language: | English |
| DOI: | 10.1038/s41594-018-0089-6 |
| PROVIDER: | scopus |
| PMCID: | PMC6082148 |
| PUBMED: | 30013099 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: 10.1038/s41594-018-0119-4 -- Article -- Export Date: 4 September 2018 -- Source: Scopus |
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